It is proposed that a study of binding interactions between three series of alpha-N-acyl-L-arginine methyl esters and one portion of the thrombin active site be initiated. The compounds will be synthesized and tested as substrates for thrombin and also for trypsin for comparison. The Michaelis constant for each molecule will be determined and used as an indication of binding affinity. Substituent constants relating to the hydrophobic, electronic, and steric properties of each analog will be correlated with the corresponding Michaelis constant using computerized regression analysis. The regression equations will be interpreted in terms of the physicochemical environment of the thrombin active site. Similar equations derived for trypsin can be used to compare the environments of these two similar active sites. Information derived from the thrombin analysis will be utilized to predict the structure of the alpha-N-acyl-L-arginine methyl ester which should bind most effectively to the thrombin active site. This structure will be used as a basis for designing a selective reversible inhibitor of thrombin.